Organotypic Models in Drug Development pp 111-141 | Cite as
Neural In Vitro Models for Studying Substances Acting on the Central Nervous System
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Abstract
Animal models have been greatly contributing to our understanding of physiology, mechanisms of diseases, and toxicity. Yet, their limitations due to, e.g., interspecies variation are reflected in the high number of drug attrition rates, especially in central nervous system (CNS) diseases. Therefore, human-based neural in vitro models for studying safety and efficacy of substances acting on the CNS are needed. Human iPSC-derived cells offer such a platform with the unique advantage of reproducing the “human context” in vitro by preserving the genetic and molecular phenotype of their donors. Guiding the differentiation of hiPSC into cells of the nervous system and combining them in a 2D or 3D format allows to obtain complex models suitable for investigating neurotoxicity or brain-related diseases with patient-derived cells. This chapter will give an overview over stem cell-based human 2D neuronal and mixed neuronal/astrocyte models, in vitro cultures of microglia, as well as CNS disease models and considers new developments in the field, more specifically the use of brain organoids and 3D bioprinted in vitro models for safety and efficacy evaluation.
Keywords
Bioprinted neuronal models Brain organoids CNS disease models Developmental neurotoxicity (DNT) Human induced pluripotent stem cells (hiPSCs) Microglia culture Neurotoxicity (NT)References
- Abernathy DG, Kim WK, McCoy MJ, Lake AM, Ouwenga R, Lee SW, Xing X, Li D, Lee HJ, Heuckeroth RO, Dougherty JD, Wang T, Yoo AS (2017) MicroRNAs induce a permissive chromatin environment that enables neuronal subtype-specific reprogramming of adult human fibroblasts. Cell Stem Cell 21:332–348.e9. https://doi.org/10.1016/j.stem.2017.08.002PubMedPubMedCentralCrossRefGoogle Scholar
- Abud EM, Ramirez RN, Martinez ES, Healy LM, Nguyen CHH, Newman SA, Yeromin AV, Scarfone VM, Marsh SE, Fimbres C, Caraway CA, Fote GM, Madany AM, Agrawal A, Kayed R, Gylys KH, Cahalan MD, Cummings BJ, Antel JP, Mortazavi A et al (2017) iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94:278–293.e9. https://doi.org/10.1016/j.neuron.2017.03.042PubMedPubMedCentralCrossRefGoogle Scholar
- Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FMV (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10:1538–1543CrossRefGoogle Scholar
- Almeida S, Zhang Z, Coppola G, Mao W, Futai K, Karydas A, Geschwind MD, Tartaglia MC, Gao F, Gianni D, Sena-Esteves M, Geschwind DH, Miller BL, Farese RV, Gao FB (2012) Induced pluripotent stem cell models of progranulin-deficient frontotemporal dementia uncover specific reversible neuronal defects. Cell Rep 2:789–798PubMedPubMedCentralCrossRefGoogle Scholar
- Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA (2011) Brief report direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Stem Cell 9:113–118. https://doi.org/10.1016/j.stem.2011.07.002CrossRefGoogle Scholar
- Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, Tietge JE, Villeneuve DL (2010) Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29:730–741PubMedCrossRefGoogle Scholar
- Antill-O’Brien N, Bourke J, O’Connell CD (2019) Layer-by-layer: the case for 3D bioprinting neurons to create patient-specific epilepsy models. Materials (Basel) 12:3218CrossRefGoogle Scholar
- Arber C, Lovejoy C, Wray S (2017) Stem cell models of Alzheimer’s disease: progress and challenges. Alzheimers Res Ther 9:1–17CrossRefGoogle Scholar
- Arcuri C, Mecca C, Bianchi R, Giambanco I, Donato R (2017) The pathophysiological role of microglia in dynamic surveillance, phagocytosis and structural remodeling of the developing CNS. Front Mol Neurosci 10:1–22CrossRefGoogle Scholar
- Bal-Price A, Crofton KM, Sachana M, Shafer TJ, Behl M, Forsby A, Hargreaves A, Landesmann B, Lein PJ, Louisse J, Monnet-Tschudi F, Paini A, Rolaki A, Schrattenholz A, Suñol C, van Thriel C, Whelan M, Fritsche E (2015) Putative adverse outcome pathways relevant to neurotoxicity. Crit Rev Toxicol 45:83–91PubMedPubMedCentralCrossRefGoogle Scholar
- Bayir E, Sendemir A, Missirlis YF (2019) Mechanobiology of cells and cell systems, such as organoids. Biophys Rev 11:721–728PubMedPubMedCentralCrossRefGoogle Scholar
- Bergmann S, Lawler SE, Qu Y, Fadzen CM, Wolfe JM, Regan MS, Pentelute BL, Agar NYR, Cho CF (2018) Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics. Nat Protoc 13:2827–2843PubMedPubMedCentralCrossRefGoogle Scholar
- Bernatchez JA, Tran LT, Li J, Luan Y, Siqueira-Neto JL, Li R (2019) Drugs for the treatment of Zika virus infection. J Med ChemGoogle Scholar
- Bhinge A, Namboori SC, Zhang X, VanDongen AMJ, Stanton LW (2017) Genetic correction of SOD1 mutant iPSCs reveals ERK and JNK activated AP1 as a driver of neurodegeneration in amyotrophic lateral sclerosis. Stem Cell Rep 8:856–869. https://doi.org/10.1016/j.stemcr.2017.02.019CrossRefGoogle Scholar
- Bian S, Repic M, Guo Z, Kavirayani A, Burkard T, Bagley JA, Krauditsch C, Knoblich JA (2018) Genetically engineered cerebral organoids model brain tumor formation. Nat Methods 15:748–748. http://www.nature.com/articles/s41592-018-0118-8PubMedPubMedCentralCrossRefGoogle Scholar
- Boissart C, Poulet A, Georges P, Darville H, Julita E, Delorme R, Bourgeron T, Peschanski M, Benchoua A (2013) Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening. Transl Psychiatry 3:e294–e211. https://doi.org/10.1038/tp.2013.71PubMedPubMedCentralCrossRefGoogle Scholar
- Boisvert EM, Engle SJ, Hallowell SE, Liu P, Wang Z (2015) The specification and maturation of nociceptive neurons from human embryonic stem cells. Nat Publ Gr:1–12. https://doi.org/10.1038/srep16821
- Bunker JM, Leslie W, Jordan MA, Feinstein SC (2004) Modulation of microtubule dynamics by tau in living cells: implications for development and neurodegeneration. Mol Biol Cell 15:2720–2728PubMedPubMedCentralCrossRefGoogle Scholar
- Camp JG, Badsha F, Florio M, Kanton S, Gerber T, Wilsch-Bräuninger M, Lewitus E, Sykes A, Hevers W, Lancaster M, Knoblich JA, Lachmann R, Pääbo S, Huttner WB, Treutlein B (2015) Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci U S A 112:15672–15677PubMedPubMedCentralCrossRefGoogle Scholar
- Carusi A, Davies MR, de Grandis G, Escher BI, Hodges G, KMY L, Whelan M, Willett C, Ankley GT (2018) Science of the total environment harvesting the promise of AOPs: an assessment and recommendations. Sci Total Environ 628–629:1542–1556. https://doi.org/10.1016/j.scitotenv.2018.02.015PubMedPubMedCentralCrossRefGoogle Scholar
- Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27:275–280. http://www.nature.com/nbt/journal/v27/n3/abs/nbt.1529.htmlPubMedPubMedCentralCrossRefGoogle Scholar
- Chang CY, Chen SM, Lu HE, Lai SM, Lai PS, Shen PW, Chen PY, Shen CI, Harn HJ, Lin SZ, Hwang SM, Su HL (2015) N-butylidenephthalide attenuates Alzheimer’s disease-like cytopathy in down syndrome induced pluripotent stem cell-derived neurons. Sci Rep 5:1–7Google Scholar
- Cheng C, Fass DM, Folz-Donahue K, MacDonald ME, Haggarty SJ (2017) Highly expandable human iPS cell-derived neural progenitor cells (NPC) and neurons for central nervous system disease modeling and high-throughput screening. Curr Protoc Hum Genet 93:21.8.1–21.8.21Google Scholar
- Cho CF, Wolfe JM, Fadzen CM, Calligaris D, Hornburg K, Chiocca EA, Agar NYR, Pentelute BL, Lawler SE (2017) Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents. Nat Commun 8:1–14. https://doi.org/10.1038/ncomms15623CrossRefGoogle Scholar
- Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D’Avanzo C, Chen H, Hooli B, Asselin C, Muffat J, Klee JB, Zhang C, Wainger BJ, Peitz M, Kovacs DM, Woolf CJ, Wagner SL, Tanzi RE, Kim DY (2014) A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature 515:274. https://doi.org/10.1038/nature13800PubMedPubMedCentralCrossRefGoogle Scholar
- Chung CY, Khurana V, Auluck PK, Tardiff DF, Mazzulli JR, Soldner F, Baru V, Lou Y, Freyzon Y, Cho S, Mungenast AE, Muffat J, Mitalipova M, Pluth MD, Jui NT, Schul̈e B, Lippard SJ, Tsai LH, Krainc D, Buchwald SL et al (2013) Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons. Science 342:983–987PubMedPubMedCentralCrossRefGoogle Scholar
- Chung SY, Kishinevsky S, Mazzulli JR, Graziotto J, Mrejeru A, Mosharov EV, Puspita L, Valiulahi P, Sulzer D, Milner TA, Taldone T, Krainc D, Studer L, won Shim J (2016) Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and α-synuclein accumulation. Stem Cell Reports 7:664–677. https://doi.org/10.1016/j.stemcr.2016.08.012PubMedPubMedCentralCrossRefGoogle Scholar
- Consortium TH iPSC (2017) Developmental alterations in Huntington’s disease neural cells and pharmacological rescue in cells and mice. Nat Neurosci 20:648–660CrossRefGoogle Scholar
- Cooper O, Seo H, Andrabi S, Guardia-Laguarta C, Graziotto J, Sundberg M, McLean JR, Carrillo-Reid L, Xie Z, Osborn T, Hargus G, Deleidi M, Lawson T, Bogetofte H, Perez-Torres E, Clark L, Moskowitz C, Mazzulli J, Chen L, Volpicelli-Daley L et al (2012) Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson’s disease. Sci Transl Med 4:141ra90PubMedPubMedCentralCrossRefGoogle Scholar
- Corti S, Nizzardo M, Simone C, Falcone M, Nardini M, Ronchi D, Donadoni C, Salani S, Riboldi G, Magri F, Menozzi G, Bonaglia C, Rizzo F, Bresolin N, Comi GP (2012) Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Sci Transl Med 4:1–32CrossRefGoogle Scholar
- Crofton KM, Mundy WR, Shafer TJ (2012) Developmental neurotoxicity testing: a path forward. Congenit Anom 52:140–146CrossRefGoogle Scholar
- Cugola FR, Fernandes IR, Russo FB, Freitas BC, Dias JLM, Guimarães KP, Benazzato C, Almeida N, Pignatari GC, Romero S, Polonio CM, Cunha I, Freitas CL, Brandaõ WN, Rossato C, Andrade DG, Faria DDP, Garcez AT, Buchpigel CA, Braconi CT et al (2016) The Brazilian Zika virus strain causes birth defects in experimental models. Nature 534:267–271PubMedPubMedCentralCrossRefGoogle Scholar
- D’Aiuto L, Zhi Y, Kumar Das D, Wilcox MR, Johnson JW, Mc Clain L, Macdonald ML, Di Maio R, Schurdak ME, Piazza P, Viggiano L, Sweet R, Kinchington PR, Bhattacharjee AG, Yolken R, Nimgaonka VL (2014) Large-scale generation of human ipsc-derived neural stem cells/early neural progenitor cells and their neuronal differentiation. Organogenesis 10:365–377PubMedCrossRefPubMedCentralGoogle Scholar
- Dai S, Li R, Long Y, Titus S, Zhao J, Huang R, Xia M, Zheng W (2016) One-step seeding of neural stem cells with vitronectin- supplemented medium for high throughput screening assays. J Biomol Screen 21:1112–1124PubMedPubMedCentralCrossRefGoogle Scholar
- Dang J, Tiwari SK, Lichinchi G, Qin Y, Patil VS, Eroshkin AM, Rana TM (2016) Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 19:258–265PubMedPubMedCentralCrossRefGoogle Scholar
- Danon JJ, Reekie TA, Kassiou M (2019) Challenges and opportunities in central nervous system drug discovery. Trends Chem 1:612–624. https://doi.org/10.1016/j.trechm.2019.04.009CrossRefGoogle Scholar
- Di Cesare ML, Pacini A, Micheli L, Tani A, Zanardelli M, Ghelardini C (2014) Glial role in oxaliplatin-induced neuropathic pain. Exp Neurol 261. https://doi.org/10.1016/j.expneurol.2014.06.016
- Djelloul M, Holmqvist S, Boza-Serrano A, Azevedo C, Yeung MS, Goldwurm S, Frisén J, Deierborg T, Roybon L (2015) Alpha-synuclein expression in the oligodendrocyte lineage: an in vitro and in vivo study using rodent and human models. Stem Cell Rep 5:174–184CrossRefGoogle Scholar
- Douvaras P, Wang J, Zimmer M, Hanchuk S, O’Bara MA, Sadiq S, Sim FJ, Goldman J, Fossati V (2014) Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells. Stem Cell Rep 3:250–259. https://doi.org/10.1016/j.stemcr.2014.06.012CrossRefGoogle Scholar
- Douvaras P, Sun B, Wang M, Kruglikov I, Lallos G, Zimmer M, Terrenoire C, Zhang B, Gandy S, Schadt E, Freytes DO, Noggle S, Fossati V (2017) Directed differentiation of human pluripotent stem cells to microglia. Stem Cell Rep 8:1516–1524. https://doi.org/10.1016/j.stemcr.2017.04.023CrossRefGoogle Scholar
- Duan L, Bhattacharyya BJ, Belmadani A, Pan L, Miller RJ, Kessler JA (2014) Stem cell derived basal forebrain cholinergic neurons from Alzheimer’s disease patients are more susceptible to cell death. Mol Neurodegener 9:1–14CrossRefGoogle Scholar
- Efthymiou A, Shaltouki A, Steiner JP, Jha B, Heman-Ackah SM, Swistowski A, Zeng X, Rao MS, Malik N (2014) Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells. J Biomol Screen 19:32–43PubMedCrossRefPubMedCentralGoogle Scholar
- Egawa N, Kitaoka S, Tsukita K, Naitoh M, Takahashi K, Yamamoto T, Adachi F, Kondo T, Okita K, Asaka I, Aoi T, Watanabe A, Yamada Y, Morizane A, Takahashi J, Ayaki T, Ito H, Yoshikawa K, Yamawaki S, Suzuki S et al (2012) Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci Transl Med 4:145ra104PubMedCrossRefPubMedCentralGoogle Scholar
- Ehrlich M, Mozafari S, Glatza M, Starost L, Velychko S, Hallmann AL, Cui QL, Schambach A, Kim KP, Bachelin C, Marteyn A, Hargus G, Johnson RM, Antel J, Sterneckert J, Zaehres H, Schöler HR, Baron-Van Evercooren A, Kuhlmann T (2017) Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors. Proc Natl Acad Sci U S A 114:E2243–E2252PubMedPubMedCentralCrossRefGoogle Scholar
- Eiraku M, Watanabe K, Matsuo-takasaki M, Kawada M, Yonemura S, Matsumura M, Wataya T, Nishiyama A, Muguruma K, Sasai Y (2008) Article self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Stem Cell 3:519–532. https://doi.org/10.1016/j.stem.2008.09.002CrossRefGoogle Scholar
- Engle SJ, Puppala D (2013) Integrating human pluripotent stem cells into drug development. Cell Stem Cell 12:669–677. https://doi.org/10.1016/j.stem.2013.05.011PubMedCrossRefPubMedCentralGoogle Scholar
- Etemad S, Zamin RM, Ruitenberg MJ, Filgueira L (2012) A novel in vitro human microglia model: characterization of human monocyte-derived microglia. J Neurosci Methods 209:79–89PubMedCrossRefPubMedCentralGoogle Scholar
- Farkhondeh A, Li R, Gorshkov K, Chen KG, Might M, Rodems S, Lo DC, Zheng W (2019) Induced pluripotent stem cells for neural drug discovery. Drug Discov Today 24:992–999. https://doi.org/10.1016/j.drudis.2019.01.007PubMedPubMedCentralCrossRefGoogle Scholar
- Flames N, Gelman DM, Rubenstein JLR, Puelles L, Marı O, Herna UM, Joan S (2007) Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J Neurosci 27:9682–9695PubMedPubMedCentralCrossRefGoogle Scholar
- Fritsche E, Barenys M, Klose J, Masjosthusmann S, Nimtz L, Schmuck M, Wuttke S, Tigges J (2018a) Current availability of stem cell-based in vitro methods for developmental neurotoxicity (DNT) testing. Toxicol Sci 165:21–30PubMedCrossRefPubMedCentralGoogle Scholar
- Fritsche E, Barenys M, Klose J, Masjosthusmann S, Nimtz L, Schmuck M, Wuttke S, Tigges J (2018b) Development of the concept for stem cell-based developmental neurotoxicity evaluation. Toxicol Sci 165:14–20. https://academic.oup.com/toxsci/article/165/1/14/5046970PubMedCrossRefPubMedCentralGoogle Scholar
- Garcez P, Loiola E, Madeiro da Costa R, Higa L, Trindade P, Delvecchio R, Nascimento J, Brindeiro R, Tanuri A, Rehen S (2016) Zika virus impairs growth in human neurospheres and brain organoids. Science 13:816–818CrossRefGoogle Scholar
- García-León JA, Cabrera-Socorro A, Eggermont K, Swijsen A, Terryn J, Fazal R, Nami FA, Ordovás L, Quiles A, Lluis F, Serneels L, Wierda K, Sierksma A, Kreir M, Pestana F, Van Damme P, De Strooper B, Thorrez L, Ebneth A, Verfaillie CM (2018a) Generation of a human induced pluripotent stem cell–based model for tauopathies combining three microtubule-associated protein TAU mutations which displays several phenotypes linked to neurodegeneration. Alzheimers Dement 14:1261–1280PubMedCrossRefPubMedCentralGoogle Scholar
- García-León JA, Kumar M, Boon R, Chau D, One J, Wolfs E, Eggermont K, Berckmans P, Gunhanlar N, de Vrij F, Lendemeijer B, Pavie B, Corthout N, Kushner SA, Dávila JC, Lambrichts I, Hu WS, Verfaillie CM (2018b) SOX10 single transcription factor-based fast and efficient generation of oligodendrocytes from human pluripotent stem cells. Stem Cell Rep 10:655–672CrossRefGoogle Scholar
- Ghaffari LT, Starr A, Nelson AT, Sattler R (2018) Representing diversity in the dish: using patient-derived in vitro models to recreate the heterogeneity of neurological disease. Front Neurosci 12:1–18CrossRefGoogle Scholar
- Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845PubMedPubMedCentralCrossRefGoogle Scholar
- Grabert K, Michoel T, Karavolos MH, Clohisey S, Kenneth Baillie J, Stevens MP, Freeman TC, Summers KM, McColl BW (2016) Microglial brain regionâ ‘dependent diversity and selective regional sensitivities to aging. Nat Neurosci 19:504–516PubMedPubMedCentralCrossRefGoogle Scholar
- Gribkoff VK, Kaczmarek LK (2017) The need for new approaches in CNS drug discovery: why drugs have failed, and what can be done to improve outcomes. Neuropharmacology 120:11–19. https://doi.org/10.1016/j.neuropharm.2016.03.021PubMedCrossRefPubMedCentralGoogle Scholar
- Guenther MG (2011) Transcriptional control of embryonic and induced pluripotent stem cells. Epigenomics 3:323–343PubMedCrossRefPubMedCentralGoogle Scholar
- Haenseler W, Sansom SN, Buchrieser J, Newey SE, Moore CS, Nicholls FJ, Chintawar S, Schnell C, Antel JP, Allen ND, Cader MZ, Wade-Martins R, James WS, Cowley SA (2017) A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response. Stem Cell Rep 8:1727–1742. https://doi.org/10.1016/j.stemcr.2017.05.017CrossRefGoogle Scholar
- Haggarty SJ, Silva MC, Cross A, Brandon NJ, Perlis RH (2016) Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models. Mol Cell Neurosci 73:104–115. https://doi.org/10.1016/j.mcn.2016.01.011PubMedPubMedCentralCrossRefGoogle Scholar
- Hall CE, Yao Z, Choi M, Tyzack GE, Serio A, Luisier R, Harley J, Preza E, Arber C, Crisp SJ, Watson PMD, Kullmann DM, Abramov AY, Wray S, Burley R, Loh SHY, Martins LM, Stevens MM, Luscombe NM, Sibley CR et al (2017) Progressive motor neuron pathology and the role of astrocytes in a human stem cell model of VCP-related ALS. Cell Rep 19:1739–1749. https://doi.org/10.1016/j.celrep.2017.05.024PubMedPubMedCentralCrossRefGoogle Scholar
- Hartfield EM, Yamasaki-Mann M, Ribeiro Fernandes HJ, Vowles J, James WS, Cowley SA, Wade-Martins R (2014) Physiological characterisation of human iPS-derived dopaminergic neurons. PLoS One 9:e87388PubMedPubMedCentralCrossRefGoogle Scholar
- Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, Becker CD, See P, Price J, Lucas D, Greter M, Mortha A, Boyer SW, Forsberg EC, Tanaka M, van Rooijen N, García-Sastre A, Stanley ER, Ginhoux F, Frenette PS et al (2013) Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38:792–804PubMedCrossRefPubMedCentralGoogle Scholar
- Hendry SH, Schwark HD, Jones EG, Yan J (1987) Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex. J Neurosci 7:1503–1519PubMedPubMedCentralCrossRefGoogle Scholar
- Hsiao HY, Chen YC, Huang CH, Chen CC, Hsu YH, Chen HM, Chiu FL, Kuo HC, Chang C, Chern Y (2015) Aberrant astrocytes impair vascular reactivity in Huntington disease. Ann Neurol 78:178–192PubMedCrossRefPubMedCentralGoogle Scholar
- Hu W, Qiu B, Guan W, Wang Q, Wang M, Li W, Gao L, Shen L (2015) Short article direct conversion of normal and Alzheimer’s disease human fibroblasts into neuronal cells by small molecules short article direct conversion of normal and Alzheimer ’ s disease human fibroblasts into neuronal cells by small molecules. Stem Cell 17:204–212. https://doi.org/10.1016/j.stem.2015.07.006CrossRefGoogle Scholar
- Huang YWA, Zhou B, Wernig M, Südhof TC (2017) ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and Aβ secretion. Cell 168:427–441.e21PubMedPubMedCentralCrossRefGoogle Scholar
- Ichida JK, Kiskinis E (2015) Probing disorders of the nervous system using reprogramming approaches. EMBO J 34:1456–1477PubMedPubMedCentralCrossRefGoogle Scholar
- Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo FS, Carson CT, Laurent LC, Marsala M, Gage FH, Remes AM, Koo EH, Goldstein LSB (2012) Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482:216–220. https://doi.org/10.1038/nature10821PubMedPubMedCentralCrossRefGoogle Scholar
- Janabi N, Peudenier S, Héron B, Ng KH, Tardieu M (1995) Establishment of human microglial cell lines after transfection of primary cultures of embryonic microglial cells with the SV40 large T antigen. Neurosci Lett 195:105–108PubMedCrossRefGoogle Scholar
- Jones VC, Atkinson-Dell R, Verkhratsky A, Mohamet L (2017) Aberrant iPSC-derived human astrocytes in Alzheimer’s disease. Cell Death Dis 8:1–11. https://doi.org/10.1038/cddis.2017.89CrossRefGoogle Scholar
- Joung D, Truong V, Neitzke CC, Guo SZ, Walsh PJ, Monat JR, Meng F, Park SH, Dutton JR, Parr AM, McAlpine MC (2018) 3D printed stem-cell derived neural progenitors generate spinal cord scaffolds. Adv Funct Mater 28:1–10Google Scholar
- Kanat O, Ertas H, Caner B (2017) Platinum-induced neurotoxicity: a review of possible mechanisms. World J Clin Oncol 8:329–336PubMedPubMedCentralCrossRefGoogle Scholar
- Karzbrun E, Kshirsagar A, Cohen SR, Hanna JH, Reiner O (2018) Human brain organoids on a chip reveal the physics of folding. Nat Phys 14:515–522PubMedPubMedCentralCrossRefGoogle Scholar
- Kayama T, Suzuki I, Odawara A, Sasaki T, Ikegaya Y (2018) Temporally coordinated spiking activity of human induced pluripotent stem cell-derived neurons co-cultured with astrocytes. Biochem Biophys Res Commun 495:1028–1033. https://doi.org/10.1016/j.bbrc.2017.11.115PubMedCrossRefPubMedCentralGoogle Scholar
- Kiskinis E, Sandoe J, Williams LA, Boulting GL, Moccia R, Wainger BJ, Han S, Peng T, Thams S, Mikkilineni S, Mellin C, Merkle FT, Davis-dusenbery BN, Ziller M, Oakley D, Ichida J, Dicostanza S, Atwater N, Maeder ML, Goodwin MJ et al (2014) Article pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Stem Cell 43:1–15. https://doi.org/10.1016/j.stem.2014.03.004CrossRefGoogle Scholar
- Klaunig JE, Babich MA, Baetcke KP, Cook JC, Corton JC, David RM, DeLuca JG, Lai DY, McKee RH, Peters JM, Roberts RA, Fenner-Crisp PA (2003) PPARα agonist-induced rodent tumors: modes of action and human relevance. Crit Rev Toxicol 33:655–780PubMedCrossRefPubMedCentralGoogle Scholar
- Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y, Imamura K, Egawa N, Yahata N, Okita K, Takahashi K, Asaka I, Aoi T, Watanabe A, Watanabe K, Kadoya C, Nakano R, Watanabe D, Maruyama K, Hori O et al (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12:487–496. https://doi.org/10.1016/j.stem.2013.01.009PubMedCrossRefGoogle Scholar
- Kriks S, Shim J, Piao J, Ganat YM, Wakeman DR, Xie Z, Carrillo-reid L (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480:547–551. https://doi.org/10.1038/nature10648PubMedPubMedCentralCrossRefGoogle Scholar
- Lancaster MA, Knoblich JA (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:1247125PubMedCrossRefGoogle Scholar
- Lancaster MA, Corsini NS, Wolfinger S, Gustafson EH, Phillips AW, Burkard TR, Otani T, Livesey FJ, Knoblich JA (2017) Guided self-organization and cortical plate formation in human brain organoids. Nat Biotechnol 35:659–666PubMedPubMedCentralCrossRefGoogle Scholar
- Lee JH, Mitchell RR, McNicol JD, Shapovalova Z, Laronde S, Tanasijevic B, Milsom C, Casado F, Fiebig-Comyn A, Collins TJ, Singh KK, Bhatia M (2015) Single transcription factor conversion of human blood fate to NPCs with CNS and PNS developmental capacity. Cell Rep 11:1367–1376. https://doi.org/10.1016/j.celrep.2015.04.056PubMedCrossRefGoogle Scholar
- Leist M, Hartung T (2013) Reprint: inflammatory findings on species extrapolations: humans are definitely no 70-kg mice1. ALTEX 30:227–230PubMedCrossRefGoogle Scholar
- Leone C, Le Pavec G, Même W, Porcheray F, Samah B, Dormont D, Gras G (2006) Characterization of human monocyte-derived microglia-like cells. Glia 54:183–192PubMedCrossRefGoogle Scholar
- Li Q, Barres BA (2018) Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol 18:225–242. https://doi.org/10.1038/nri.2017.125PubMedPubMedCentralCrossRefGoogle Scholar
- Li Y, Muffat J, Omer A, Bosch I, Lancaster MA, Sur M, Gehrke L, Knoblich JA, Jaenisch R (2017) Induction of expansion and folding in human cerebral organoids. Cell Stem Cell 20:385–396.e3. https://doi.org/10.1016/j.stem.2016.11.017PubMedPubMedCentralCrossRefGoogle Scholar
- Lindborg BA, Brekke JH, Vegoe AL, Ulrich CB, Haider KT, Subramaniam S, Venhuizen SL, Eide CR, Orchard PJ, Chen W, Wang Q, Pelaez F, Scott CM, Kokkoli E, Keirstead SA, Dutton JR, Tolar J, O’Brien TD (2016) Rapid induction of cerebral organoids from human induced pluripotent stem cells using a chemically defined hydrogel and defined cell culture medium. Stem Cells Transl Med 5:970–979. https://doi.org/10.5966/sctm.2015-0305PubMedPubMedCentralCrossRefGoogle Scholar
- Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang S (2013) Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat Protoc 8:1670–1679. https://doi.org/10.1038/nprot.2013.106PubMedPubMedCentralCrossRefGoogle Scholar
- Lopez-Gonzalez R, Lu Y, Gendron TF, Karydas A, Tran H, Yang D, Petrucelli L, Miller BL, Almeida S, Gao FB (2016) Poly(GR) in C9ORF72-related ALS/FTD compromises mitochondrial function and increases oxidative stress and DNA damage in iPSC-derived motor neurons. Neuron 92:383–391. https://doi.org/10.1016/j.neuron.2016.09.015PubMedPubMedCentralCrossRefGoogle Scholar
- Lowry WE, Plath K (2008) The many ways to make an iPS cell. Nat Biotechnol 26:1246–1248PubMedCrossRefGoogle Scholar
- Lundin A, Delsing L, Clausen M, Ricchiuto P, Sanchez J, Sabirsh A, Ding M, Synnergren J, Zetterberg H, Brolén G, Hicks R, Herland A, Falk A (2018) Human iPS-derived astroglia from a stable neural precursor state show improved functionality compared with conventional astrocytic models. Stem Cell Rep 10:1030–1045. https://linkinghub.elsevier.com/retrieve/pii/S221367111830047XCrossRefGoogle Scholar
- Malik N, Efthymiou AG, Mather K, Chester N, Wang X, Nath A, Rao MS, Steiner JP (2014) Compounds with species and cell type specific toxicity identified in a 2000 compound drug screen of neural stem cells and rat mixed cortical neurons. Neurotoxicology 45:192–200PubMedPubMedCentralCrossRefGoogle Scholar
- Manabe T, Tatsumi K, Inoue M, Matsuyoshi H, Makinodan M, Yokoyama S, Wanaka A (2005) L3/Lhx8 is involved in the determination of cholinergic or GABAergic cell fate. J Neurochem 94:723–730PubMedCrossRefGoogle Scholar
- Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L, Amenduni M, Szekely A, Palejev D, Wilson M, Gerstein M, Grigorenko EL, Chawarska K, Pelphrey KA, Howe JR, Vaccarino FM (2015) FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders. Cell 162:375–390PubMedPubMedCentralCrossRefGoogle Scholar
- Masjosthusmann S, Barenys M, El-Gamal M, Geerts L, Gerosa L, Gorreja A, Kühne B, Marchetti N, Tigges J, Viviani B, Witters H, Fritsche E (2018) Literature review and appraisal on alternative neurotoxicity testing methods. EFSA Support Publ 15:1–108Google Scholar
- Massaro EJ (2002) Handbook of neurotoxicology. Springer Science + Business Media, New YorkCrossRefGoogle Scholar
- Matsui TK, Matsubayashi M, Sakaguchi YM, Hayashi RK, Zheng C, Sugie K, Hasegawa M, Nakagawa T, Mori E (2018) Six-month cultured cerebral organoids from human ES cells contain matured neural cells. Neurosci Lett 670:75–82. https://doi.org/10.1016/j.neulet.2018.01.040PubMedCrossRefGoogle Scholar
- Maury Y, Côme J, Piskorowski RA, Salah-Mohellibi N, Chevaleyre V, Peschanski M, Martinat C, Nedelec S (2015) Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes. Nat Biotechnol 33:89–96PubMedCrossRefGoogle Scholar
- McComish SF, Caldwell MA (2018) Generation of defined neural populations from pluripotent stem cells. Philos Trans R Soc B Biol Sci 373:20170214CrossRefGoogle Scholar
- McQuade A, Coburn M, Tu CH, Hasselmann J, Davtyan H, Blurton-Jones M (2018) Development and validation of a simplified method to generate human microglia from pluripotent stem cells. Mol Neurodegener 13:1–13CrossRefGoogle Scholar
- Mertens J, Reid D, Lau S, Kim Y, Gage FH (2018) Aging in a dish: iPSC-derived and directly induced neurons for studying brain aging and age-related neurodegenerative diseases. Annu Rev Genet 52:271–293PubMedPubMedCentralCrossRefGoogle Scholar
- Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, Bakiasi G, Tsai LH, Aubourg P, Ransohoff RM, Jaenisch R (2016) Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med 22:1358–1367PubMedPubMedCentralCrossRefGoogle Scholar
- Muratore CR, Rice HC, Srikanth P, Callahan DG, Shin T, Benjamin LNP, Walsh DM, Selkoe DJ, Young-Pearse TL (2014) The familial alzheimer’s disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum Mol Genet 23:3523–3536PubMedPubMedCentralCrossRefGoogle Scholar
- Nagai A, Mishima S, Ishida Y, Ishikura H, Harada T, Kobayashi S, Kim SU (2005) Immortalized human microglial cell line: phenotypic expression. J Neurosci Res 81:342–348PubMedCrossRefGoogle Scholar
- Naghieh S, Sarker MD, Abelseth E, Chen X (2019) Indirect 3D bioprinting and characterization of alginate scaffolds for potential nerve tissue engineering applications. J Mech Behav Biomed Mater 93:183–193PubMedCrossRefGoogle Scholar
- National Institute of Health Neurotoxicity Information (2019). https://www.ninds.nih.gov/disorders/all-disorders/neurotoxicity-information-page#disorders-r1
- Nehme R, Zuccaro E, Ghosh SD, Fu Z, Ghosh SD, Li C, Sherwood JL, Pietilainen O (2018) Combining NGN2 programming with developmental patterning generates human excitatory neurons with NMDAR-mediated synaptic transmission resource combining NGN2 programming with developmental patterning generates human excitatory neurons with NMDAR-mediated. Cell Rep 23:2509–2523. https://doi.org/10.1016/j.celrep.2018.04.066PubMedPubMedCentralCrossRefGoogle Scholar
- Nzou G, Wicks RT, Wicks EE, Seale SA, Sane CH, Chen A, Murphy SV, Jackson JD, Atala AJ (2018) Human cortex spheroid with a functional blood brain barrier for high-throughput neurotoxicity screening and disease modeling. Sci Rep 8:1–10. https://doi.org/10.1038/s41598-018-25603-5CrossRefGoogle Scholar
- Oksanen M, Petersen AJ, Naumenko N, Puttonen K, Lehtonen Š, Gubert Olivé M, Shakirzyanova A, Leskelä S, Sarajärvi T, Viitanen M, Rinne JO, Hiltunen M, Haapasalo A, Giniatullin R, Tavi P, Zhang SC, Kanninen KM, Hämäläinen RH, Koistinaho J (2017) PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer’s disease. Stem Cell Rep 9:1885–1897CrossRefGoogle Scholar
- Oliveira LMA, Falomir-Lockhart LJ, Botelho MG, Lin KH, Wales P, Koch JC, Gerhardt E, Taschenberger H, Outeiro TF, Lingor P, Schüle B, Arndt-Jovin DJ, Jovin TM (2015) Elevated α-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson’s patient-derived induced pluripotent stem cells. Cell Death Dis 6:1–13Google Scholar
- Ormel PR, Vieira de Sá R, van Bodegraven EJ, Karst H, Harschnitz O, Sneeboer MAM, Johansen LE, van Dijk RE, Scheefhals N, Berdenis van Berlekom A, Ribes Martínez E, Kling S, MacGillavry HD, van den Berg LH, Kahn RS, Hol EM, de Witte LD, Pasterkamp RJ (2018) Microglia innately develop within cerebral organoids. Nat Commun 9:4167. https://doi.org/10.1038/s41467-018-06684-2PubMedPubMedCentralCrossRefGoogle Scholar
- Osaki T, Shin Y, Sivathanu V, Campisi M, Kamm RD (2018) In vitro microfluidic models for neurodegenerative disorders. Adv Healthc Mater 7Google Scholar
- Paini A, Leonard JA, Joossens E, Bessems JGM, Desalegn A, Dorne JL, Gosling JP, Heringa MB, Klaric M, Kliment T, Kramer NI, Loizou G, Louisse J, Lumen A, Madden JC, Patterson EA, Proenca S, Punt A, Setzer RW, Suciu N et al (2019) Next generation physiologically based kinetic (NG-PBK) models in support of regulatory decision making. Comput Toxicol (Amsterdam, Netherlands) 9:61–72Google Scholar
- Pandya H, Shen MJ, Ichikawa DM, Sedlock AB, Choi Y, Johnson KR, Kim G, Brown MA, Elkahloun AG, Maric D, Sweeney CL, Gossa S, Malech HL, McGavern DB, Park JK (2017) Differentiation of human and murine induced pluripotent stem cells to microglia-like cells. Nat Neurosci 20:753–759PubMedPubMedCentralCrossRefGoogle Scholar
- Park DY, Lee J, Chung JJ, Jung Y, Kim SH (2019) Integrating organs-on-chips: multiplexing, scaling, vascularization, and innervation. Trends Biotechnol 38:99–112. https://doi.org/10.1016/j.tibtech.2019.06.006PubMedCrossRefPubMedCentralGoogle Scholar
- Pasca SP (2018) The rise of three-dimensional human brain cultures. Nature 553:437–445. https://doi.org/10.1038/nature25032PubMedCrossRefGoogle Scholar
- Patani R, Lewis PA, Trabzuni D, Puddifoot CA, Wyllie DJA, Walker R, Smith C, Hardingham GE, Weale M, Hardy J, Chandran S, Ryten M (2012) Investigating the utility of human embryonic stem cell-derived neurons to model ageing and neurodegenerative disease using whole-genome gene expression and splicing analysis. J Neurochem 122:738–751PubMedPubMedCentralCrossRefGoogle Scholar
- Pérez-Cerdá F, Sánchez-Gómez MV, Matute C (2015) Pío del Río hortega and the discovery of the oligodendrocytes. Front Neuroanat 9:7–12CrossRefGoogle Scholar
- Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, Yao B, Hamersky GR, Jacob F, Zhong C, Yoon KJ, Jeang W, Lin L, Li Y, Thakor J, Berg DA, Zhang C, Kang E, Chickering M, Nauen D et al (2016) Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165:1238–1254. https://doi.org/10.1016/j.cell.2016.04.032PubMedPubMedCentralCrossRefGoogle Scholar
- Qian X, Nguyen HN, Jacob F, Song H, Ming GL (2017) Using brain organoids to understand Zika virus-induced microcephaly. Dev 144:952–957CrossRefGoogle Scholar
- Quadrato G, Nguyen T, Macosko EZ, Sherwood JL, Min Yang S, Berger DR, Maria N, Scholvin J, Goldman M, Kinney JP, Boyden ES, Lichtman JW, Williams ZM, McCarroll SA, Arlotta P (2017) Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545:48–53. http://www.nature.com/articles/nature22047PubMedPubMedCentralCrossRefGoogle Scholar
- Raja WK, Mungenast AE, Lin YT, Ko T, Abdurrob F, Seo J, Tsai LH (2016) Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer’s disease phenotypes. PLoS One 11:1–18CrossRefGoogle Scholar
- Rana P, Luerman G, Hess D, Rubitski E, Adkins K, Somps C (2017) Toxicology in vitro utilization of iPSC-derived human neurons for high-throughput drug- induced peripheral neuropathy screening. Toxicol Vitr 45:111–118. https://doi.org/10.1016/j.tiv.2017.08.014CrossRefGoogle Scholar
- Ransohoff RM, El Khoury J (2016) Microglia in health and disease. Cold Spring Harb Perspect Biol 8:a020560. http://cshperspectives.cshlp.org/lookup/doi/10.1101/cshperspect.a020560PubMedCentralCrossRefPubMedGoogle Scholar
- Rindt H, Tom CM, Lorson CL, Mattis VB (2017) Optimization of trans-splicing for Huntington’s disease RNA therapy. Front Neurosci 11:1–13CrossRefGoogle Scholar
- Ryan KJ, White CC, Patel K, Xu J, Olah M, Replogle JM, Frangieh M, Cimpean M, Winn P, McHenry A, Kaskow BJ, Chan G, Cuerdon N, Bennett DA, Boyd JD, Imitola J, Elyaman W, De Jager PL, Bradshaw EM (2017) A human microglia-like cellular model for assessing the effects of neurodegenerative disease gene variants. Sci Transl Med 9:1–13CrossRefGoogle Scholar
- Sahara S, Yanagawa Y, O’Leary DDM, Stevens CF (2012) The fraction of cortical GABAergic neurons is constant from near the start of cortical neurogenesis to adulthood. J Neurosci 32:4755–4761PubMedPubMedCentralCrossRefGoogle Scholar
- Sanchez-Danes A, Richaud-patin Y, Carballo-carbajal I, Sa A, Caig C, Mora S, Di Guglielmo C, Ezquerra M, Vila M, Cuervo AM, Tolosa E, Consiglio A, Raya A (2012) Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol Med 4:380–395PubMedPubMedCentralCrossRefGoogle Scholar
- Sareen D, Ebert AD, Heins BM, McGivern JV, Ornelas L, Svendsen CN (2012) Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy. PLoS One 7:e39113PubMedPubMedCentralCrossRefGoogle Scholar
- Sareen D, O’Rourke JG, Meera P, Muhammad AKMG, Grant S, Simpkinson M, Bell S, Carmona S, Ornelas L, Sahabian A, Gendron T, Petrucelli L, Baughn M, Ravits J, Harms MB, Rigo F, Bennett CF, Otis TS, Svendsen CN, Baloh RH (2013) Targeting RNA foci in iPSC-derived motor neurons from ALS patients with C9ORF72 repeat expansion. Sci Transl Med 5:1–57CrossRefGoogle Scholar
- Schröter F, Sleegers K, Van Cauwenberghe C, Bohndorf M, Wruck W, Van Broeckhoven C, Adjaye J (2016) Lymphoblast-derived integration-free iPSC lines from a female and male Alzheimer’s disease patient expressing different copy numbers of a coding CNV in the Alzheimer risk gene CR1. Stem Cell Res 17:560–563. https://doi.org/10.1016/j.scr.2016.10.003PubMedCrossRefPubMedCentralGoogle Scholar
- Seidel D, Jahnke H, Englich B, Girard M, Robitzki AA (2017) In vitro field potential monitoring on a multi-microelectrode array for the electrophysiological long-term screening of neural stem cell maturation. Analyst 142:1929–1937. http://xlink.rsc.org/?DOI=C6AN02713JPubMedCrossRefPubMedCentralGoogle Scholar
- Sellgren CM, Sheridan SD, Gracias J, Xuan D, Fu T, Perlis RH (2017) Patient-specific models of microglia-mediated engulfment of synapses and neural progenitors. Mol Psychiatry 22:170–177PubMedCrossRefPubMedCentralGoogle Scholar
- Sherman SP, Bang AG (2018) High-throughput screen for compounds that modulate neurite growth of human induced pluripotent stem cell-derived neurons. DMM Dis Model Mech 11:dmm031906PubMedCrossRefPubMedCentralGoogle Scholar
- Shi Y, Kirwan P, Smith J, MacLean G, Orkin SH, Livesey FJ (2012) A human stem cell model of early Alzheimer’s disease pathology in down syndrome. Sci Transl Med 4:124ra29. https://doi.org/10.1016/j.jalz.2012.05.1946PubMedPubMedCentralCrossRefGoogle Scholar
- Shi Y, Kirwan P, Smith J, Robinson HPC, Livesey FJ (2014) Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat Neurosci 15:1–25. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3882590&tool=pmcentrez&rendertype=abstractGoogle Scholar
- Shi Y, Inoue H, Wu JC, Yamanaka S (2017) Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16:115–130PubMedCrossRefGoogle Scholar
- Silva MC, Haggarty SJ (2019) Human pluripotent stem cell–derived models and drug screening in CNS precision medicine. Ann N Y Acad SciGoogle Scholar
- Singh VK, Kalsan M, Kumar N, Saini A, Chandra R (2015) Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol 3:1–18CrossRefGoogle Scholar
- Stacey P, Wassermann AM, Kammonen L, Impey E, Wilbrey A, Cawkill D (2018) Plate-based phenotypic screening for pain using human iPSC-derived sensory neurons. SLAS Disc 23:585–596Google Scholar
- Suga M, Kondo T, Inoue H (2019) Modeling neurological disorders with human pluripotent stem cell-derived astrocytes. Int J Mol Sci 20:9–14CrossRefGoogle Scholar
- Szlachcic WJ, Switonski PM, Krzyzosiak WJ, Figlerowicz M, Figiel M (2015) Huntington disease iPSCs show early molecular changes in intracellular signaling, the expression of oxidative stress proteins and the p53 pathway. Dis Model Mech 8:1047–1057PubMedPubMedCentralCrossRefGoogle Scholar
- Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. http://www.ncbi.nlm.nih.gov/pubmed/18035408CrossRefGoogle Scholar
- Thomson JA, Itskovitz-eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1148PubMedCrossRefGoogle Scholar
- Toutain P-L, Ferran A, Bousquet-Melou A (2010) Species differences in pharmacokinetics and pharmacodynamics. Handb Exp Pharmacol:19–48Google Scholar
- Tukker AM, De Groot MWGDM, Wijnolts FMJ, Kasteel EEJ, Hondebrink L, Westerink RHS (2016) Research article is the time right for in vitro neurotoxicity testing using human iPSC-derived neurons? ALTEX 33:261–271PubMedPubMedCentralGoogle Scholar
- Tukker AM, Wijnolts FMJ, de Groot A, Westerink RHS (2018) Neurotoxicology human iPSC-derived neuronal models for in vitro neurotoxicity assessment. Neurotoxicology 67:215–225. https://doi.org/10.1016/j.neuro.2018.06.007PubMedCrossRefPubMedCentralGoogle Scholar
- Victor MB, Richner M, Hermanstyne TO, Ransdell JL, Sobieski C, Deng P, Klyachko VA, Nerbonne JM, Yoo AS (2014) NeuroResource generation of human striatal neurons by MicroRNA-dependent direct conversion of fibroblasts. Neuron 84:311–323. https://doi.org/10.1016/j.neuron.2014.10.016PubMedPubMedCentralCrossRefGoogle Scholar
- Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463:1035–1041PubMedPubMedCentralCrossRefGoogle Scholar
- von Bartheld CS, Bahney J, Herculano-houzel S (2017) The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. J Comp Neurol 524:3865–3895CrossRefGoogle Scholar
- Wang S, Bates J, Li X, Schanz S, Chandler-militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA (2013) Clinical progress progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Stem Cell 12:252–264. https://doi.org/10.1016/j.stem.2012.12.002CrossRefGoogle Scholar
- Wang C, Ward ME, Chen R, Liu K, Tracy TE, Chen X, Xie M, Sohn PD, Ludwig C, Meyer-Franke A, Karch CM, Ding S, Gan L (2017) Scalable production of iPSC-derived human neurons to identify Tau-Lowering compounds by high-content screening. Stem Cell Rep 9:1221–1233. https://doi.org/10.1016/j.stemcr.2017.08.019CrossRefGoogle Scholar
- Wapinski OL, Lee QY, Chen AC, Li R, Corces MR, Ang CE, Treutlein B, Xiang C, Baubet V, Suchy FP, Sankar V, Sim S, Quake SR, Dahmane N, Wernig M, Chang HY (2017) Rapid chromatin switch in the direct reprogramming of fibroblasts to neurons. Cell Rep 20:3236–3247PubMedPubMedCentralCrossRefGoogle Scholar
- Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618–630PubMedPubMedCentralCrossRefGoogle Scholar
- Watanabe M, Buth JE, Vishlaghi N, de la Torre-Ubieta L, Taxidis J, Khakh BS, Coppola G, Pearson CA, Yamauchi K, Gong D, Dai X, Damoiseaux R, Aliyari R, Liebscher S, Schenke-Layland K, Caneda C, Huang EJ, Zhang Y, Cheng G, Geschwind DH et al (2017) Self-organized cerebral organoids with human-specific features predict effective drugs to combat Zika virus infection. Cell Rep 21:517–532. https://doi.org/10.1016/j.celrep.2017.09.047PubMedPubMedCentralCrossRefGoogle Scholar
- Woodruff G, Young JE, Martinez FJ, Buen F, Gore A, Kinaga J, Li Z, Yuan SH, Zhang K, Goldstein LSB (2013) The Presenilin-1 δE9 mutation results in reduced γ-secretase activity, but not total loss of PS1 function, in isogenic human stem cells. Cell Rep 5:974–985. https://doi.org/10.1016/j.celrep.2013.10.018PubMedCrossRefPubMedCentralGoogle Scholar
- Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, Tcw J, Kouznetsova J, Ogden SC, Hammack C, Jacob F, Nguyen HN, Itkin M, Hanna C, Shinn P, Allen C, Michael SG, Simeonov A, Huang W, Christian KM et al (2016) Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med 22:1101–1107PubMedPubMedCentralCrossRefGoogle Scholar
- Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T, Yamanaka S, Okano H, Suzuki N (2011) Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum Mol Genet 20:4530–4539PubMedCrossRefPubMedCentralGoogle Scholar
- Yahata N, Asai M, Kitaoka S, Takahashi K, Asaka I, Hioki H, Kaneko T, Maruyama K, Saido TC, Nakahata T, Asada T, Yamanaka S, Iwata N, Inoue H (2011) Anti-Aβ drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer’s disease. PLoS One 6:e25788PubMedPubMedCentralCrossRefGoogle Scholar
- Yang N, Chanda S, Marro S, Ng YH, Janas JA, Haag D, Ang CE, Tang Y, Flores Q, Mall M, Wapinski O, Li M, Ahlenius H, Rubenstein JL, Chang HY, Buylla AA, Südhof TC, Wernig M (2017) Generation of pure GABAergic neurons by transcription factor programming. Nat Methods 14:621–628. https://doi.org/10.1038/nmeth.4291PubMedPubMedCentralCrossRefGoogle Scholar
- Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, Lee-Messer C, Dometsch RE, Tsien RW, Crabtree GR (2011) MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476:228–231. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdfPubMedPubMedCentralCrossRefGoogle Scholar
- Young JE, Boulanger-Weill J, Williams DA, Woodruff G, Buen F, Revilla AC, Herrera C, Israel MA, Yuan SH, Edland SD, Goldstein LSB (2015) Elucidating molecular phenotypes caused by the SORL1 Alzheimer’s disease genetic risk factor using human induced pluripotent stem cells. Cell Stem Cell 16:373–385. https://doi.org/10.1016/j.stem.2015.02.004PubMedPubMedCentralCrossRefGoogle Scholar
- Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920PubMedCrossRefGoogle Scholar
- Yu J, Hu K, Smuga-otto K, Tian S, Stewart R, Igor I, Thomson JA (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801PubMedPubMedCentralCrossRefGoogle Scholar
- Yu D, Swaroop M, Wang M, Baxa U, Yang R, Yan Y, Coksaygan T, DeTolla L, Marugan JJ, Austin CP, Mckew JC, Gong D-W, Zheng W (2014) Niemann-Pick disease type C: induced pluripotent stem cell- derived neuronal cells for modeling neural disease and evaluating drug efficacy. J Biomol Screen 19:1164–1173PubMedPubMedCentralCrossRefGoogle Scholar
- Zhang Y, Pak CH, Han Y, Ahlenius H, Zhang Z, Chanda S, Marro S, Patzke C, Acuna C, Covy J, Xu W, Yang N, Danko T, Chen L, Wernig M, Südhof TC (2013) Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78:785–798PubMedPubMedCentralCrossRefGoogle Scholar
- Zhou T, Tan L, Cederquist GY, Fan Y, Hartley BJ, Mukherjee S, Tomishima M, Brennand KJ, Zhang Q, Schwartz RE, Evans T, Studer L, Chen S (2017) High-content screening in hPSC-neural progenitors identifies drug candidates that inhibit Zika virus infection in fetal-like organoids and adult brain. Cell Stem Cell 21:274–283.e5. https://doi.org/10.1016/j.stem.2017.06.017PubMedPubMedCentralCrossRefGoogle Scholar
- Zhuang X, Lu C (2016) PBPK modeling and simulation in drug research and development. Acta Pharm Sin B 6:430–440PubMedPubMedCentralCrossRefGoogle Scholar